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Midazolam suppresses thrombin‐induced heat shock protein 27 phosphorylation through inhibition of p38 mitogen‐activated protein kinase in cardiac myocytes
Author(s) -
Tanabe Kumiko,
Akamatsu Shigeru,
Suga Hidetaka,
Takai Shinji,
Kato Kanefusa,
Dohi Shuji,
Kozawa Osamu
Publication year - 2005
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20455
Subject(s) - hsp27 , thrombin , phosphorylation , p38 mitogen activated protein kinases , protein kinase a , mitogen activated protein kinase kinase , ask1 , mitogen activated protein kinase , kinase , microbiology and biotechnology , map kinase kinase kinase , map2k7 , chemistry , heat shock protein , biology , cyclin dependent kinase 2 , biochemistry , hsp70 , platelet , immunology , gene
It has been shown that anesthetics have effects of cardiac preconditioning. Heat shock proteins (HSPs) function as molecular chaperone. Among them, HSP27, a low‐molecular‐weight HSP, abundantly exist in heart. However, the relationship between anesthetics and HSP27 in heart is not yet clarified. We investigated whether thrombin induces or phosphorylates HSP27 in primary cultured mouse myocytes and the effect of midazolam on the thrombin‐stimulated HSP27 phosphorylation and the mechanism behind it. Thrombin time dependently phosphorylated HSP27 at Ser‐15 and Ser‐85 while having no effect on the levels of HSP27. Midazolam markedly suppressed the thrombin‐induced phosphorylation of HSP27 at both Ser‐15 and Ser‐85. Thrombin induced the phosphorylation of p44/p42 MAP kinase and p38 MAP kinase without affecting stress‐activated protein kinase/c‐ Jun N ‐terminal kinase. In addition, midazolam attenuated the phosphorylation of thrombin‐induced p38 MAP kinase but not that of p44/p42 MAP kinase. SB203580 and PD169316, inhibitors of p38 MAP kinase, suppressed the thrombin‐induced phosphorylation of HSP27 at both Ser‐15 and Ser‐85. These results strongly suggest that thrombin induces the HSP27 phosphorylation at least through the p38 MAP kinase activation in cardiac myocytes and that midazolam inhibits the thrombin‐induced HSP27 phosphorylation via suppression of p38 MAP kinase activation. © 2005 Wiley‐Liss, Inc.